金匮肾气丸对多囊卵巢综合征模型大鼠的改善作用及机制研究
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篇名: 金匮肾气丸对多囊卵巢综合征模型大鼠的改善作用及机制研究
TITLE: Study on improvement effects of Jinkui shenqi pills on polycystic ovary syndrome model rats and the mechanism
摘要: 目的 探讨金匮肾气丸对多囊卵巢综合征(PCOS)模型大鼠的改善作用及机制。方法将40只大鼠灌胃来曲唑混悬液(1mg/kg,每天1次,连续21d)复制PCOS模型。将造模成功的大鼠分为模型组、炔雌醇环丙孕酮片(简称“达英-35”)+二甲双胍组(达英-350.2mg/kg+二甲双胍230mg/kg,阳性对照)和金匮肾气丸低、中、高剂量组(0.5、1.0、2.0g/kg),每组10只。另取10只未造模大鼠作为正常组。各组大鼠灌胃相应药物,每天1次,连续30d。末次灌胃24h后,检测大鼠血清中血糖、胰岛素、雌二醇(E2)、睾酮(T)、促性腺激素释放激素(GnRH)、促卵泡素(FSH)和促黄体生成素(LH)水平,并计算胰岛素抵抗指数;计算大鼠卵巢系数;观察大鼠卵巢组织的病理形态学变化;检测大鼠卵巢组织中肝激酶B1(LKB1)、腺苷酸活化蛋白激酶(AMPK)蛋白和mRNA的表达水平。结果与正常组比较,模型组大鼠血糖、胰岛素水平,胰岛素抵抗指数,血清中T、GnRH、LH水平,卵巢系数均显著升高(P<0.05),血清中E2、FSH水平及卵巢组织中LKB1、AMPK蛋白和mRNA表达水平均显著降低(P<0.05);卵巢皮质胶原化,闭锁卵泡和无卵丘的囊性卵泡数量增多,可见卵泡囊性病变。与模型组比较,金匮肾气丸各剂量组大鼠上述大部分指标水平均显著逆转(P<0.05);金匮肾气丸中、高剂量组大鼠卵巢组织内各级卵泡数量增多,未见卵泡囊性病变。结论金匮肾气丸对PCOS模型大鼠性激素水平异常、胰岛素抵抗及卵巢囊性改变均有较好的改善作用,其作用机制可能与上调LKB1/AMPK信号通路活性有关。
ABSTRACT: OBJECTIVE To investigate the improvement effects of Jinkui shenqi pills on polycystic ovary syndrome (PCOS) model rats and the mechanism. METHODS Totally 40 rats were given letrozole suspension instragastrically (1 mg/kg, once a day, for consecutive 21 d) to induce PCOS model. Model rats were divided into model group, ethinylestradiol and cyproterone acetate tablets (short for diane-35)+metformin group (diane-35 0.2 mg/kg + metformin 230 mg/kg, as positive control), Jinkui shenqi pills low-dose, medium-dose and high-dose groups (0.5, 1.0, 2.0 g/kg), with 10 rats in each group. Other 10 healthy rats were included in normal group. Each group was given the corresponding drugs, once a day, for consecutive 30 d. Twelve hours after the last administration, serum levels of blood glucose, insulin, estrogen (E2), testosterone (T), gonadotropin-releasing hormone (GnRH), follicle-stimulating hormone (FSH) and luteinizing hormone (LH) were measured. The insulin resistance indexes were calculated, and the ovary coefficients of rats were calculated. The pathological changes of ovary were observed. The protein and mRNA expressions of liver kinase B1 (LKB1) and AMP-activated protein kinase (AMPK) in ovary tissue were detected. RESULTS Compared with normal group, the levels of blood glucose, insulin, insulin resistance index, serum levels of T, GnRH and LH and ovarian indexes were significantly increased (P<0.05), while serum levels of E2 and FSH as well as protein and mRNA expressions of LKB1 and AMPK in ovary tissue were decreased significantly (P<0.05); collagenization of ovarian cortex, increased number of atresia follicles and cystic follicles without cumulus, and follicular cystic lesions could be seen. Compared with model group, most of above indexes of Jinkui shenqi pills groups were reversed significantly (P<0.05); the number of follicle at each level was increased and no follicular cystic lesion was found in Jinkui shenqi pills medium-dose and high-dose groups. CONCLUSIONS Jinkui shenqi pills can significantly improve the abnormal level of sex hormones, insulin resistance and 222102310139) ovarian cystic changes, the mechanism of which may be related to up-regulating the activation of LKB1/AMPK signaling pathway.
期刊: 2022年第33卷第23期
作者: 马丽亚,杜婧雯,张童,俎兆轩,郭申,赵绅,张明昊
AUTHORS: MA Liya,DU Jingwen,ZHANG Tong,ZU Zhaoxuan,GUO Shen,ZHAO Shen,ZHANG Minghao
关键字: 金匮肾气丸;多囊卵巢综合征;胰岛素抵抗;LKB1/AMPK信号通路;大鼠
KEYWORDS: Jinkui shenqi pills; polycystic ovary syndrome;
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